PUBLICATION
Liver-specific androgen receptor knockout attenuates early liver tumor development in zebrafish
- Authors
- Li, H., Li, Y., Lu, J.W., Huo, X., Gong, Z.
- ID
- ZDB-PUB-190725-6
- Date
- 2019
- Source
- Scientific Reports 9: 10645 (Journal)
- Registered Authors
- Gong, Zhiyuan
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Carcinogenesis/metabolism*
- Carcinoma, Hepatocellular/metabolism*
- Cell Proliferation/genetics
- Disease Models, Animal
- Disease Progression
- Female
- Gene Knockout Techniques
- Liver/metabolism*
- Liver Neoplasms/metabolism*
- Male
- Proto-Oncogene Proteins p21(ras)/genetics
- Receptors, Androgen/genetics*
- Receptors, Androgen/metabolism
- Zebrafish/genetics*
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 31337771 Full text @ Sci. Rep.
Citation
Li, H., Li, Y., Lu, J.W., Huo, X., Gong, Z. (2019) Liver-specific androgen receptor knockout attenuates early liver tumor development in zebrafish. Scientific Reports. 9:10645.
Abstract
Hepatocellular carcinoma (HCC) is one of the most severe cancer types and many genetic and environmental factors contribute to the development of HCC. Androgen receptor (AR) signaling is increasingly recognized as one of the important factors associated with HCC. Previously, we have developed an inducible HCC model in kras transgenic zebrafish. In the present study, to investigate the role of AR in liver tumor development, we specifically knocked out ar gene in the liver of zebrafish via the CRISPR/Cas9 system and the knockout zebrafish was named L-ARKO for liver-specific ar knockout. We observed that liver-specific knockout of ar attenuated liver tumor development in kras transgenic zebrafish at the early stage (one week of tumor induction). However, at the late stage (two weeks of tumor induction), essentially all kras transgenic fish continue to develop HCC irrespective of the absence or presence of ar gene, indicating an overwhelming role of the driver oncogene kras over ar knockout. Consistently, cell proliferation was reduced at the early stage, but not the late stage, of liver tumor induction in the kras/L-ARKO fish, indicating that the attenuant effect of ar knockout was at least in part via cell proliferation. Furthermore, androgen treatment showed acceleration of HCC progression in kras fish but not in kras/L-ARKO fish, further indicating the abolishment of ar signalling. Therefore, we have established a tissue-specific ar knockout zebrafish and it should be a valuable tool to investigate AR signalling in the liver in future.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping